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▎Edited by WuXi AppTec Content Team  

The emergence of immune checkpoint inhibitors (ICI) has changed the landscape of cancer treatment. ICI therapy targeting PD-1/PD-L1 or CTLA-4 has shown effective tumor clearance in a variety of cancer types. At present, ICI therapy still faces some key challenges, one of which is how to increase the proportion of patients who effectively respond to therapy and reduce the occurrence of secondary drug resistance.

In addition to looking for ways to enhance ICI from the outside, there is another available helper coming from within humans. In 2021, Science magazine reported that some melanoma patients responded well to ICI, while others had almost no response, and this degree of response to the drug may come from differences in the microbiome.They tried to transplant fecal microbiota from patients who responded well to ICIs into patients who responded poorly, and found that the latter also benefited from ICIs.。Researchers believe that specific bacteria in the transplanted fecal flora can activate the function of T cells and change the conditions of the tumor microenvironment, allowing ICI to work better.

Recently, in a smallClinical TrialsIn the study, scientists from the Gwangju Institute of Science and Technology in South Korea once again demonstrated that fecal microbiota transplantation (FMT) has the potential to enhance ICI therapy.Cell Host & MicrobeThe results showed that 13 patients participating in the trial included three types of cancer: gastric cancer, esophageal cancer and hepatocellular carcinoma, all of whom received fecal microbiota transplantation from individuals who had a durable response to ICI therapy.Among them, 6 patients benefited from FMT. When combined with ICI therapy, cancer progression was controlled and the tumor volume of some patients was significantly reduced.。

Volunteers participating in the trial were recruited in 2019-2020. They were initially treated with the PD-1 inhibitor nivolumab but still showed signs of cancer progression. Some patients did not respond to nivolumab from the beginning, while others quickly developed drug resistance.

Subsequently, the researchers decided to continue to give the patient nivolumab and add FMT treatment.The stool samples came from individuals who had long-term responses to nivolumab, with complete or partial responses lasting more than 1 year after treatment.

▲Research diagram(Image source: Reference [1])

In the trial, volunteers will first receive antibiotic treatment to suppress and eliminate their original microbiome, and then complete FMT through colonoscopy. During the observation period, volunteers experienced few adverse events, only one patient developed immune-related gastritis, and some patients had symptoms of rash and skin itching.

Overall, after FMT was added to ICI treatment, 5 of the 13 volunteers had stable disease symptoms, 1 volunteer achieved partial remission, and the objective disease control rate reached 46.2%. Among them, a patient with hepatocellular carcinoma showed the most unique performance. He still had cancer progression after the first FMT treatment, so the researchers replaced his fecal flora sample with another donor.The second FMT produced a significant therapeutic effect, with the patient's tumor size shrinking by 30.5% after 8 weeks of treatment.。

▲Patients with hepatocellular carcinoma can benefit significantly from ICI treatment after FMT, and the tumor volume is significantly reduced.(Image source: Reference [1])